Subcutaneous Hemodynamic Monitoring Devices, Systems and Methods

ABSTRACT

An implantable sensor system using one or more sensor implants comprised of micro-electrical mechanical system (MEMS) sensors for the accurate and continuous measurement of physiological hemodynamic signals such as diastolic and systolic blood pressure. Sensor implants are configured to be subcutaneously injected to a placement site adjacent a blood vessel. In some embodiments, sensors comprise micromachined ultrasonic transducers.

RELATED APPLICATIONS

This application is a division of U.S. application Ser. No. 17/493,500,filed on Oct. 4, 2021, and titled “Injectable Hemodynamic MonitoringDevices, Systems and Methods” (now U.S. Pat. No.______), which is acontinuation of PCT Application No. PCT/US2021/033138, filed on May 19,2021, and titled “Injectable Hemodynamic Monitoring Devices, Systems andMethods”; which international application claims priority to U.S.Provisional Application No. 63/026,878, filed May 19, 2020, entitled“Injectable Blood Pressure Monitoring Systems and Methods”. Each ofthese applications is incorporated herein in its entirety.

FIELD

The present disclosure generally relates to the field of miniaturizedimplantable vital signs monitoring devices and methods. In particular,the present disclosure is directed to subcutaneously placeable bloodpressure monitoring systems and methods suitable, inter alia, forlong-term monitoring of cardiovascular signals.

BACKGROUND

Hypertension is a significant precursor to cardiovascular disease anddeath. It is estimated that there are 1.6 billion people worldwide withhypertension, over 100 million in the United States alone, and less thanone-third are under control. Hypertension is costly and deadly. Thereare an estimated 7.8 million deaths each year due to hypertension, andit costs the United States an estimated $131 billion annually due tolost productivity and healthcare costs. Due to its deadliness and costs,it has been a target of government, academic, for-profit, and non-profitorganizations. A recent task force has been formed to help reduce theincidence and prevalence of hypertension.

While there are many effective therapies and management protocols toprevent the progression of cardiovascular disease, patients andclinicians are challenged to achieve optimal management for a variety ofreasons. First, hypertension is largely asymptomatic. Patients are oftenunaware they have hypertension which creates skepticism and doubtwhether they need to take their prescribed medications or follow dietand exercise recommendations. Secondly, doctors only have sporadic,point-in-time data with varying accuracy of the measurement taken whenit is taken outside the clinic. When measurements are taken in a clinicsetting, patients may experience either White Coat Syndrome, or MaskedHypertension. This lack of consistent and accurate blood pressure dataand trends decreases confidence in the right medical managementdecisions. Clinicians do not have enough data to make an accuratetherapeutic change that could benefit the patient.

Current practices to improve blood control status and management includehome blood pressure monitoring and ambulatory blood pressure monitoring.Many patients use, and clinicians prescribe, home blood pressuremonitors to augment in-clinic measurements. These traditional home bloodpressure monitors are point-in-time and require the patient to takeaction regularly, and to have cognitive physical ability to accuratelyplace the blood pressure cuff and collect multiple measurements that canbe averaged to filter out inaccuracies or outliers. Another challengewith traditional home blood pressure monitoring is that it does notallow a patient to take their blood pressure at night for obviousreasons. It is also not possible to capture blood pressure readingsduring different activities compared to resting. Clinical research hasdemonstrated the clinical relevance and importance of day vs. nightblood pressure and the relationship to when medications areadministered.

Another prescribed technology is Ambulatory Blood Pressure Monitoring(ABPM). Recent FDA approvals and CMS coverage decisions for ABPM arepromising and the technology addresses some of the challenges oftraditional home blood pressure monitoring systems. But the technologycontinues to be a barrier to patient and physician adoption. ABPMtechnology available today uses traditional sphygmomanometer methods tocapture blood pressure measurements every 15 minutes for a period of24-48 or even 72 hours. While the patient can be “ambulatory”, thepatient wears a cuff that inflates as often as every 15 minutescontinuously for up to 72 hours causing pain and bruises. It keeps thepatient awake at night, and it is an inconvenient system to wear duringactivities or even during a working day. It is intrusive into thepatient's life and indiscreet.

Accordingly, there remains a clinical need for effective and minimallyinvasive and minimally intrusive methods to monitor and track bloodpressure continuously over time.

SUMMARY

In one implementation, the present disclosure is directed to ahemodynamic sensor system, which includes a sensor implant, comprising ahousing configured and dimensioned to be placed subcutaneously in tissueadjacent a target blood vessel in a patient, the sensor implant furthercomprising within the housing: at least one sensor configured to detectone or more physiological parameters indicative of patient hemodynamiccondition, wherein at least one the sensor comprises an at least oneultrasound transducer; and a communication module communicating with theat least one sensor to transmit one or more signals comprising signalsrepresentative of detected physiological parameters to an externalreceiver.

In another implementation, the present disclosure is directed to ahemodynamic sensor system, which includes a sensor implant configured tobe implanted in patient tissue adjacent a target blood vessel, whereinthe sensor implant comprises: a housing having a housing axis; at leasttwo ultrasound transducers disposed in the housing along the housingaxis with a known distance along the housing axis between the at leasttwo ultrasound transducers, each the ultrasound transducer positioned todetect a change in diameter of the target blood vessel in response to acardiac pulse and produce signals representative of detected changes indiameter; at least one accelerometer disposed in the housing configuredto detect movement or changes in position of the patient and producesignals representative of the movement or changes in position; acontroller disposed in the housing configured to detect timing of andprocess the signals from the ultrasound transducers and the at least oneaccelerometer to produce a data stream from which pulse wave velocityfor the target blood vessel and patient blood pressure can becalculated; a communication module disposed in the housing configured totransmit the data stream to an external receiver; and a power sourcedisposed in the housing operatively connected to power the sensorimplant.

In yet another implementation, the present disclosure is directed to ahemodynamic sensor system, which includes a sensor implant configuredand dimensioned to be placed subcutaneously in tissue adjacent a targetblood vessel in a patient, the sensor implant comprising at least onesensor configured to generate a data stream from which pulse wavevelocity of the target blood vessel during a sensing period can bedetermined, and a communication module communicating with the at leastone sensor to wirelessly transmit the data stream; and a computingdevice configured to receive data contained within the data stream anddetermine pulse wave velocity for the target blood vessel and bloodpressure for the patient using the received data.

In still another implementation, the present disclosure is directed to ahemodynamic sensor system, which includes a sensor implant configuredand dimensioned to be placed subcutaneously within tissue adjacent atarget blood vessel in a patient, the sensor implant comprising a firstultrasound transducer configured and controlled to send pulses andreceive pulse echoes representing inner and outer walls of the targetblood vessel at a first sensing location, and to generate first datarepresentative of the first sensing location pulse echoes, at least asecond ultrasound transducer spaced from the first ultrasound transducerconfigured and controlled to send pulses and receive pulse echoesrepresenting inner and outer walls of the target blood vessel at asecond sensing location, and to generate second data representative ofthe second sensing location pulse echoes, an accelerometer configured todetect patient movement, and to generate third data representative ofdetected movement, a temperature sensor configured to detect patienttemperature, and to generate fourth data representative of detectedtemperature, and a communication module configured to receive the dataand wirelessly transmit the data; a local control module external to thepatient configured to wirelessly receive and relay the data transmittedby the communication module; a user interface configured to receive userinput patient specific information comprising at least an initialpatient diastolic blood pressure; and a computing device configured toreceive the data from the local control module and the user inputpatient specific information, and to execute an instruction set todetermine pulse wave velocity for the target blood vessel and bloodpressure for the patient using the data and input patient specificinformation.

BRIEF DESCRIPTION OF DRAWINGS

For the purpose of illustrating the disclosure, the drawings showaspects of one or more embodiments of the disclosure. However, it shouldbe understood that the present disclosure is not limited to the precisearrangements and instrumentalities shown in the drawings, wherein:

FIG. 1 is a schematic depiction of an overall system according to anembodiment of the present disclosure.

FIG. 2 is block diagram illustrating functional modules of sensors asdisclosed herein.

FIGS. 2A, 2B and 2C are block diagrams illustrating in more detailfunctional modules of alternative embodiments of sensors.

FIG. 3 is a block diagram illustrating principle functional componentsin embodiments of sensor implants disclosed herein.

FIG. 3A is sensor state diagram for an embodiment of a sensor module ofthe present disclosure.

FIG. 3B is schematic illustration of a sensor element array for a pMUTor cMUT sensor module as disclosed herein.

FIG. 4 is a schematic depiction of a first embodiment of a sensoraccording to the present disclosure.

FIG. 5 is a schematic depiction of a second embodiment of a sensoraccording to the present disclosure.

FIG. 6 is a schematic depiction of a third embodiment of a sensoraccording to the present disclosure.

FIG. 7 is a schematic depiction of deployment of a first sensorembodiment as disclosed herein.

FIG. 8 is a schematic cross-section of a delivery device for a secondsensor embodiment as disclosed herein.

FIG. 8A is a schematic cross-section of the delivery device of FIG. 8 ina partially deployed state.

FIG. 8B is a schematic cross-section of the delivery device of FIG. 8 ina further partially deployed state.

FIG. 8C is a schematic perspective view of the delivery device of FIG. 8in a partially deployed state.

FIG. 9 is schematic depiction of an embodiment of an implant sensorafter deployment as in FIGS. 8 through 8C.

FIG. 10 is a schematic cross-section of the delivery device for thefirst sensor embodiment as disclosed herein.

FIG. 10A is a schematic cross-section of the delivery device for thefirst sensor embodiment as in FIG. 10 in a partially deployed state.

FIG. 10B is a schematic cross-section of the delivery device for thefirst sensor embodiment as in FIG. 10 in a further partially deployedstate.

FIG. 11 is a combined schematic and block diagram illustrating sensingand signal processing according to embodiments of the presentdisclosure.

FIG. 12 is an illustration of a sample of the pulse echoes produced by adual array sensor implant configured in accordance with the presentdisclosure.

FIG. 13 is a flow diagram illustrating a signal processing methodologyaccording to an embodiment of the present disclosure.

FIG. 14 is a schematic depiction of another system according to analternative embodiment of the present disclosure FIG. 15 is a blockdiagram illustrating components of computing devices which may be usedto execute various aspects of the present disclosure.

FIG. 16 presents FIG. 3 of Ma, et al., Relation between blood pressureand pulse wave velocity for human arteries, cited in full andincorporated by reference hereinbelow, showing four different curvesillustrating the relationships between blood pressure and pulse wavevelocity (PWV) under various wherein (A) shows normalized blood pressureP versus normalized PWV for the human artery characterized by the Funghyperelastic model. (B-D); normalized P versus normalized PWV for (B)different axial stretching of the artery; (C) differentthickness-to-radius ratio h0=R0 of the artery, and (D) different SD afor a normal distribution of h0=R0.

DETAILED DESCRIPTION

Embodiments of the present disclosure provide unobtrusive, minimallyinvasive, active implantable sensor devices, sensor systems and methodsthat meet current clinical needs. Disclosed devices, systems and methodsuse one or more micro-electrical mechanical system (MEMS) sensors forthe accurate and continuous measurement of physiological hemodynamicsignals such as diastolic and systolic blood pressure. In certainvariations, embodiments disclosed herein may include any, or all, of thefollowing additional clinical signals of overall patient status: heartrate, activity level (patient movement or position), temperature, heartrate variability, and stenosis. Disclosed embodiments can provide along-term sensor system will provide accurate (equivalent to currentstandard of care) blood pressure over an extended duration (forinstance, months or years), enabling the clinician to provideappropriate treatment recommendations.

The use of microelectromechanical systems (MEMS) manufacturingtechniques in disclosed embodiments provides a unique micro-sizeddesign, construction, and fixation that allows the implanted sensorsystem to be fixated just outside the target blood vessel wall, or insome alternatives in the vessel wall, using methods familiar toclinicians trained in accessing a blood vessel (such asultrasound-guided imaging, and standard needle and syringe access toartery) and minimally invasive outpatient procedures. MEMS construction,unique materials and resultant miniaturized design also promotesefficient use of power compared to more conventional ultrasoundtransducers. Typical sizes of disclosed sensor implants are millimetersize scale; for example, in some embodiments sensor implant size willhave dimensions ranging from about 1 mm to about 30 mm in any of length,width and height directions, and more typically may be in the range2.5-7.5 mm width×15-30 mm length×2-4 mm height. Novel injection toolsenable the sensor implant to be inserted in an outpatient or clinicsetting within minutes. A benefit of a clinic setting is that thepatient acceptance increases, and more physicians will beskilled/trained in the minimally invasive procedure.

Persons skilled in the art will appreciate various features andadvantages of devices, systems and methods of the present disclosure,including, but not limited to active implant (battery or inductivelypowered) to help reduce patient compliance challenges; fixationmechanism that allows the sensor system to be injected, but fixatedoutside the artery (in some embodiments, e.g. extravascular) to helpreduce thrombus that can lead to signal drift and decreased sensitivity,minimize dislodgement, and clot adverse events compared to anintravascular sensor; MEMS-based-sensor module that incorporates one ormore of sensors (strain/piezoelectric resistive transducer,piezoelectric/capacitive ultrasound); biocompatible nano-coatings tominimize encapsulation/biofouling; and ability to continuously captureand store cardiovascular signals for an extended duration.

As illustrated in FIG. 1 , components of a basic system 100 according tothe present disclosure may comprise injectable sensor implant 102,injection device 104, local control module 106, network-based analyticsand data management modules 108 and clinician module 110 comprising userinterfaces/applications for data access, analysis and alerts. Localcontrol module 106 may take a variety of forms. In some embodiments,module 106 may comprise simply a communications module, facilitatingcommunication between sensor implant 102 and network-based modules 108and/or clinician module 110. In other embodiments, in addition to acommunications sub-module, local module 106 may include processingand/or data storage sub-modules configured to store patient data fromsensor implant 102 and/or determine patient parameters, such as bloodpressure and fluid status, as described herein below. Module 106 alsomay function as an edge device for communication with network-basedanalytics, storage and data management modules. Module 106 thus maycomprise one or more processors, memories and associated computingcomponents commensurate with the functionality of module 106 in aspecific configuration as may be devised by persons skilled in the artbased on the teachings of the present disclosure. In some embodiments,local control module 106 may comprise a personal mobile device, such asa cell phone or tablet, running a downloadable app.

Clinician module 110 may comprise wirelessly connected devices such ascomputers, cell phones or tablets. Clinician module 110 also may beconfigured as a patient interface. In some embodiments, particularlywhere configured as a patient interface, module 110 may comprise an apprunning on the same device as running an app for local module 106. Insome embodiments, the functionality of both modules 106 and 110 may beincorporated into a single app executed on a mobile device.

Wireless communication links 112 a and 112 b are provided between sensorimplant 102, local module 106 and network-based analytics or datamanagement modules 108. Communication link 112 b also may comprise awired communication link. Communication links 113 between local module106 and user interfaces 110 may be wired or wireless. Additionally,clinician module 110 may communicate directly with network-basedanalytics module 108. Communication links 112 a, 112 b and 113 maycomprise any of a number of known communication protocols. For example,communication link 112 a may comprise a personal area network (PAN)using communications based on technologies such as IrDA, Wireless USB,Bluetooth or ZigBee. Communication links 112 b, 113 may comprise longerrange, larger bandwidth communications such as LAN, WLAN or IAN. In afurther alternative embodiment, one or more sensor implants 102 maycommunicate wirelessly with other sensor types of sensor modules via abody area network (BAN).

As shown in FIG. 2 , sensor implants 102 according to the presentdisclosure may generally comprise a layered MEMS structure withtypically three functional layers made up of functional modules andsub-modules: power supply and communication layer 114 comprisingelements such as a primary cell batteries conventionally used to powermicro-sized medical implants or, in some embodiments, a solid statelithium ion rechargeable battery and RF antenna for charging andcommunication, ASIC and memory layer 116 comprising amplifiers, filters,processing and memory storage, and sensor layer 118 comprising one ormore sensor modules, which may comprise piezoelectric micromachinedultrasonic transducers (pMUT) or capacitive micromachined ultrasonictransducers (cMUT). In some embodiments, capacitive pressure sensing maybe employed. Other sensing modules may be configured as patient statussensors with additional sensing capabilities as described herein below.Functional layers 114, 116 and 118, together comprise a sensor packagecontained within a biocompatible housing 120. In some embodiments, powersupply and communication layer 114 may be configured for inductivecoupling for charging and/or communications.

The layered MEMS structures described herein provide actively powered,integrated sensor implants well-suited to long-term sub-cutaneous andextravascular monitoring of blood pressure and other cardiovascularvital signs using ultrasound (US). The disclosed structures thus addresschallenges of previous approaches to collect reliable continuous bloodpressure over time. FIGS. 2A, 2B and 2C illustrate a number ofalternative configurations for sensor implant 102 that achieve theseadvantages.

Sensor implant 102 a, shown in FIG. 2A, includes power module 121 andcommunications module 122 in functional layer 114. In some embodimentswhere inductive power coupling is used as the power source, the powermodule 121 and communications module 122 may be integrated as a singlecommunications/power source module. Control and signal processing module123 resides in functional layer 116. In this embodiment, MUT sensorarray 124, along with status sensor module 130 and optional acousticlens 125 comprise sensor layer 118. This layered MEMS structure iscontained within biocompatible housing 120. In some embodiments, housing120 may comprise rigid materials such as titanium, stainless steel ornitinol. Biocompatible plastics or silicone also may be used as ahousing material. If the material for housing 120 is not freelytransmissive of US signals, one or more appropriate US transmissivewindow(s) 127 may be provided aligned with US sensor array 124, suchthat housing 120 may comprise non-US transmissive portions 126 andtransmissive portions 127. Materials for US transmissive window(s) 127include biocompatible materials such as polydimethylsiloxane (PDMS),silicone, glass, ceramic or parylene coatings.

Outer surfaces of housing 126 may be provided with a coating ofmaterials to promote tissue adhesion, such as collagen, fibrin,chitosan, hyaluronic acid, and alginate, and/or may have textured,roughened or featured surfaces for this purpose. Other surfaces, such asUS transmissive windows 127, may have coatings to prevent tissueadhesion. Examples of adhesion preventative coatings include polymerbrushes and self-assembled monolayers. As shown in FIG. 2A, fixationfeatures 128 may comprise three-dimensional surface irregularitiesdesigned to create friction and prevent device migration over time.These irregularities may be rigid structures or compliant structures,such as fabric mesh or loops. In other embodiments, retractable tineswith memory and flexibility (nitinol) are optimally placed to promotestable implant position over time. Fixation tines are collapsible andare collapsed inside of an insertion tool and engage when released fromthe insertion tool. Alternatively, one or more wings, or flaps, areoptimally placed to promote stable implant position over time, and maybe configured to collapse when inside the insertion tool and engage whenreleased from the insertion tool. In some embodiments, fixation features128 also may be configured as antennas as a part of communicationsmodule 122. Sensor implants 102 also may include an attachment andrelease feature 129 on an outer surface of housing 126. Attachment andrelease feature 129 may comprise a loop or recess that is releasablyengageable by a delivery and retrieval mechanism as described in moredetail below.

As indicated in FIG. 2A, extravascular sensor implants according to thepresent disclosure are preferably positioned at a known distance fromthe outer wall of the blood vessel (BV) to be interrogated. Optimumplacement distance from the blood vessel may be set by persons ofordinary skill based on the teachings of the present disclosure takinginto account parameters such as a sensor array configuration, tuning ofthe US signal using system electronics and selection of an acousticlens. An advantage of injection devices 104 hereinafter described isthat they allow for precise placement at a preferred sensing distanceusing visualization such as external ultrasound visualization. In someembodiments, sensing distance from the blood vessel outer wall will bein the range of about 2 mm to about 50 mm. In other embodiments, anarrower distance range of about 3 mm to about 15 mm may be preferableand, in some cases, a placement of 5 mm to 7 mm may be ideal.

While sensor implant 102 a includes only a single sensor array 124,often it will be preferable to include at least two, spaced-apart sensorarrays 124 in order to facilitate pulse wave velocity (PWV) measurementsas in sensor implant 102 b, shown in FIG. 2B. Sensor implant 102 b isconfigured substantially the same as sensor implant 102 a, with theexception of the accommodation of two sensor arrays 124 andcorresponding two US transmissive windows 127. Alternatively, ratherthan discrete windows, the two ends of the sensor implant may betransparent and comprised of material that supports ultrasound andcommunication. Examples of such materials include polydimethylsiloxane(PDMS), silicone, glass and ceramic. In a further alternative, theentire housing 120 may comprise a US transparent material that alsopermits transmission of communications signals from the antennastructure of communication module 122.

FIG. 2C illustrates a further alternative embodiment, including multiple(N1 through Nn) sensor arrays 124, wherein sensor implant 102 c isentirely a flexible construction including housing 120 being made offlexible material that also permits US signal transmission andcommunication signal transmission from communication module 122. Anexample of such a housing material includes certain polymers andceramic. Flexible functional layers 114, 116 and 118 may be fabricatedusing carbon nanotubes or ultrathin silicon integrated circuittechnologies. FIG. 2C also illustrates a further alternative fixationfeature 128, in the form of micro hooks. Such hooks may be comprised ofresilient materials such as nitinol wire or biocompatible fabrics formedas hooks of hook and loop fasteners material.

Embodiments of sensor implants disclosed herein are physically arrangedin a manner to promote accurate readings regardless of migration orchanges in orientation after implantation. This will include acombination of unique sensor fabrication that physically orientstransducers in a fashion that will maintain focus on vessel of interestregardless of modest migration or movement of sensor away from vessel ofinterest. Aspects of this physical arrangement include the elongatedconfiguration of housing 126 with plural spaced-apart sensor arrays 124positioned on one side of the sensor implant, with appropriatelypositioned fixation features 128. These aspects of the disclosed sensorspresent a unique advantage over prior systems by making PWV calculationsand blood pressure calculations based on the PWV calculations possibleusing only a single, unitary sensor implant to provide not only allnecessary timing and dimensional data at two spaced-apart locations, butalso, in some embodiments, additional patient position and movement datato allow more accurate assessment of patient hemodynamic state, andblood pressure in particular.

FIG. 3 presents a representative block diagram of major functionalblocks within embodiments of implant sensors 102 as disclosed herein. Asshown therein, power module 121 provides a power source in the form of apower supply comprising battery 131 and power management sub-module 132.Note that the battery can be generalized to any suitable implantableprimary cell or rechargeable power source as may be devised by personsof ordinary skill. Power management sub-module 132 is configured forbattery optimization to power US wireless communication, etc., with norequired patient interaction to power the device, which is a substantialimprovement over prior devices. Long-term monitoring can be achievedthrough the application of algorithms that reduce power consumptionduring idle times and optimize overall battery consumption, includingdetecting power requirements and automatedly switching appropriatemodules or sub-modules to “power off” mode when power is not required inthose modules or sub-modules.

Communications module 122 comprises a transceiver sub-module configuredfor the selected communications mode and corresponding antenna, which ispreferably positioned opposite the sensor modules at or through housing120. In some embodiments, the antenna may comprise fixation features 128(e.g., FIGS. 2A-C). Control and signal processing module 123 maycomprise memory 133, digital control 134, transmit and receiveelectronics sub-module 135, data converter 137 and processing sub-module136 including at least one microprocessor. These components may beconfigured by persons skilled in the art based on the teachingscontained herein. As will be appreciated, sensor integration with ASICprovides efficiency gains in power and size by integrating the MEMSsensor into the ASIC design. While in some embodiments pulse wavevelocity and patient blood pressure may be calculated within sensorimplant 102, it may be preferable to configure processing module 123with instructions to produce a data stream from which pulse wavevelocity for the blood vessel and patient blood pressure (optionallyalso heart rate) can be calculated.

Status sensor module 130 may comprise one or a collection of severaldifferent sensor types, including but not limited to inertialmeasurement unit (IMU), accelerometer, temperature sensor, electrodesfor ECG or impedance, and oxygen saturation. Status sensor module 130thus provides for monitoring of a number of different physiologicparameters, such as temperature, body position, activity, ECG and fluidretention, to compliment blood pressure measurements to assist inassessment of patient's overall condition. In most embodiments, at leasta status sensor module with an accelerometer will be included to allowthe data stream produced by control and processing module 123 to includeinformation needed to adjust the blood pressure calculation tocompensate for patient position and/or movement.

FIG. 3A illustrates sensor array state configurations. When multiplesensor arrays are employed, for example as in sensor implant 102 c,shown in FIG. 2C, with each additional sensor array, its operation stateduring use (Tx or Rx) is flexible. As an example, a configuration whereSensor N1 and Sensor N2 are present is shown in FIG. 3A, wherein eachsensor array has options of receive, transmit and active switchingbetween receive and transmit. Sensor state is programmable viaelectronics sub-module 135.

A two-dimensional representation of a cMUT or pMUT array is shown inFIG. 3B. In this example, sensor module 124 comprises substrate 138 withan array of sensor elements 139. Ideally, the array parameters, Ds(sensor element diameter), Hs (array height) and Ls (array length), areoptimized for performance within a specific sensor implant and system.For example, Ds is preferably selected based at least in part on adesired frequency of operation, thus defining a minimum vessel diameterchange that can be detected by the sensor implant. Hs and Ls definenumber of sensor elements and are selected at least in part to optimizesignal-to-noise ratio (SNR) as the pulse echo amplitude is defined bythese parameters. Sensor array size can also be selected in combinationwith the number of plural sensor modules (as in, for example, sensorimplant 102 c (FIG. 2C) in order to facilitate position identificationand compensation as discussed below. In some embodiments a preferredmaterial for sensor array 138/139 is aluminium nitride (AlN), whichprovides US power-efficient and biocompatible sensor array substratecompatible with human implantation. Previous lead-based ultrasoundtransducers require 100× more energy to power sensor and are also notbiocompatible for implantable use in living beings. Further details ofMUT sensor constructs suitable for use in sensor implants according tothe present disclosure can be found, for example, in U.S. Pat. No.10,864,553, granted Dec. 15, 2020, entitled “Piezoelectric transducersand methods of making and using the same,” and U.S. Pat. No. 10,820,888,granted Nov. 3, 2020, entitled “Miniature ultrasonic imaging system,”each of which is incorporated by reference herein in its entirety.

A variety of alternative embodiments of sensor package form-factor anddelivery systems will now be described in more detail with reference toFIGS. 4 through 10B. In one alternative embodiment, shown in FIG. 4 ,sensor implant 102 d comprises housing 120 containing a sensor packageas described in various embodiments above. Sensor implant 102 d includestissue-engaging tines as fixation features 128 for securing the implantin proximity to blood vessel (BV) within which measurements are to bemade. Tissue-engaging tines as fixation features 128 may be configuredto engage and anchor in tissues such as muscle tissue, skin tissue,outer layers of the blood vessel itself or other suitable tissues insufficient proximity to the vessel in which measurements are to be made.The tines may have barbs or other retention features (not shown) toincrease the anchoring function.

In another alternative embodiment, shown in FIG. 5 , injectable sensor102 e may utilize a passive anchor system as fixation feature 128. Inthis example, resilient cuff as fixation feature 128 engages around theblood vessel (BV) and thus positions sensor housing 120 in closeproximity to the blood vessel (BV) or in contact therewith. A method anddeployment device for a resilient cuff-type fixation feature is shown inFIGS. 8-8C and described in more detail below.

In yet another alternative embodiment, shown in FIG. 6 , sensor implant102 f comprises housing 120 with fixation feature 128 comprised ofanchor element 140 disposed on the end of flexible member 141 extendingfrom the sensor housing. In this arrangement, housing 120 of sensorimplant 102 f may be disposed on the inside of the blood vessel (BV)with flexible member 141 extending through the blood vessel wall, cappedwith anchor element 140. This arrangement may also allow the use ofalternative sensor types requiring contact with the fluid to bemeasured, such as MEMS capacitive sensors. Sensor implant 102 f may beplaced with instrumentation and procedures as used for vascularelectrode placement or for certain vascular closure devices havinganchor member placed within the vascular lumen.

FIG. 7 shows deployment may be accomplished with alternative injectiondevice 104 a, including an outer sheath 142 with a sharpened,needle-like distal end terminating in a shovel-like protective extension143. Injection device 104 a otherwise may in general be configuredsimilar to a larger-sized syringe device, wherein only the distal endportion is shown in FIG. 7 . Outer sheath 142 is inserted through tissuesuch that protective shovel portion 143 is disposed at the intendeddeployment site. Tether 144 serves as both a pusher and retrieval memberfor deployment of sensor 102 d including anchoring tines as shown inFIG. 4 . When the distal end of injection device 104 a is properlypositioned, tether 144 is used to move sensor 102 d to an exposedposition over shovel-like extension 143. This allows the tines formingfixation feature 128 of sensor 102 d to engage overlying tissue whileprotecting the blood vessel disposed below shovel-like projection 143.Tether 144 may then be disengaged and with the tines of sensor 102 dengaged on overlying tissue, injection device 104 a may be withdrawn.Alternatively, if positioning is not as desired, tether 144 may be usedto draw sensor 102 d back within sheath 142 for repositioning. Tether144 may engage with attachment and release feature 129 as previouslydescribed. Outer sheath 142, shown in FIG. 7 with a slight distal bend,may alternatively be straight.

FIGS. 8, 8A-C and 9 illustrate an embodiment of injection device 150,configured for delivering an injectable sensor such as sensor 102 e(FIG. 5 ) utilizing a resilient cuff as a passive fixation feature 128.Injection device 150 is configured generally as a syringe-type devicewith an outer introducer 152 surrounding an inner sheath 154 having aresiliently curved distal tip. Device injector 156 (e.g. a pusher) isconcentrically disposed in the center lumen of inner sheath 154 andcomprises a release and retrieval mechanism with a hook at the distalend 157 that opens and closes to release or grab sensor 102 e as needed.In one embodiment the release mechanism may comprise pull wire 158 (FIG.8B).

After the distal end of introducer 152 is positioned subcutaneously inthe area of deployment, inner sheath 154 is extended and its resilientcurvature causes it to wrap around the BV at the site of interest asshown in FIGS. 8C and 9 . Device injector 156 is used to position ormaintain sensor 102 e at the distal end of inner sheath 154 as itsurrounds the blood vessel. Once positioned as shown in FIG. 8C, innersheath 154 may be withdrawn to expose sensor 102 e as in FIG. 9 .Resilient anchor cuff 128 then surrounds the blood vessel (BV) whilestill secured to device injector 156 by retrieval mechanism hook 157.Optionally, position may be confirmed by visualization such as byultrasound or fluoroscopy. With sensor 102 e and cuff 128 positionedaround the blood vessel at the site of interest, hook 157 may bedisengaged by pulling release wire 158. In some embodiments, atraumaticpassive ball 160 may be disposed on the end of cuff 128 opposite sensorhousing 120. Anchor cuff 128 may be made of resilient, shape-memorymaterials such as nitinol.

FIGS. 10, 10A and 10B illustrate a further alternative injection device170 suitable for placement of a number of different sensor implants 102at monitoring locations in tissue adjacent to targeted blood vesselsaccording to the present disclosure. As shown therein, injection device170 comprises outer introducer 172 with a sharpened, needle orsyringe-like distal end, an inner atraumatic curved sheath 174 anddevice injector 176 sliding within inner sheath 174. Injection device170 is also generally configured as a syringe-type device. In order todeploy sensor implant 102 with injection device 170, introducer 172 ispositioned subcutaneously at the desired location, preferably undervisualization, such as with ultrasound. When appropriate positioning isconfirmed, inner sheath 174 is advanced out of the distal end ofintroducer 172. Atraumatic distal end of inner sheath 174 facilitatespositioning in close proximity to a blood vessel of interest whileminimizing possibility of trauma to the blood vessel during the sensorinjection procedure. Distal end of inner sheath 174 may have a pre-setcurve as shown in FIGS. 10A and 10B such that after exiting outerintroducer the inner sheath automatically assumes the pre-set curvaturethereby facilitating placement with reduced risk of trauma to theadjacent blood vessel. After inner sheath 174 is properly positioned,sensor 102 is advanced out of the distal end by device injector 176. Thedistal end of device injector 176 may be provided with a retrievalmechanism such as a hook as described herein. After position of sensor102 and engagement of the fixation feature is confirmed, inner sheath174 may be withdrawn and then the sensor disengaged from device injector176. Injection device 170 as a whole is then withdrawn.

FIG. 11 illustrates the use of MEMS ultrasound in sensor implant 102 todetermine blood pressure and other vitals based on pulse transit timeand pulse wave velocity measurements 180, which are amplified, filteredand processed 182 to provide a data stream from which blood pressureover time 184 may be calculated according to known correlations betweenblood pressure and pulse wave velocity. Ultrasound is the transmissionof sound waves through a medium. When the ultrasound sound waves reach asurface or differing medium, the wave reflects and travels back in theoriginating direction. The time it takes for the ultrasound wave totravel can be used to calculate the distance from the reflectingsurface. This ultrasound concept may be used in embodiments of thepresent disclosure to calculate the diameter of the vessel wall and canbe used to estimate volumetric changes in the vessel as a pulse wavetravels through the vessel. Based on the wave transmission andproperties, the ability to differentiate the variability in reflectingmediums, such as hard plaque or wall stiffness, is also possible.

One example of known algorithms for blood pressure calculation on thisbasis is described by Ma, et al., Relation between blood pressure andpulse wave velocity for human arteries, Proc. Natl. Acad. Sci. USA, 2018Oct. 30; 115(44):11144-11149 (doi:10.1073/pnas.1814392115), Epub 2018Oct. 15 (incorporated by reference herein in its entirety). In in vitroexperiments, Ma, et al. have validated correlation of pulse wavevelocity (PWV) to blood pressure through the integral of the innerartery radius to the outer artery radius after artery deformation(before and after the pulse travels through the artery). As described inMa, et al., for the human artery wall well-characterized by the Funghyperelastic model, with the energy density described as

$\begin{matrix}{{W = {{\frac{C}{2}e^{{a_{1}E_{00}^{2}} + {a_{2}E_{22}^{2}}}} - \frac{C}{2}}},} & \left\lbrack {{Ma}{Equation}9} \right\rbrack\end{matrix}$

given artery geometry parameters ho and Ro, the artery materialconstants C, a₁ and ρ are known. And whose normalized blood pressure, P,versus normalized pulse wave velocity, PWV follows the FIG. 16 , curveA, relationship between P and PWV is described by

P=aPWV ²+β,  [Ma equation 18]

whereby, both expressions for constants α and β are derived from thesymbolic solution of

$\begin{matrix}{{{\ln\frac{P}{C}} + {\ln\left( {\sqrt{1 + {\frac{8\rho}{a_{1}}\frac{{PWV}^{2}}{P}}} - 1} \right)}} = {\frac{a_{1}}{16}\left( {\sqrt{1 + {\frac{8\rho}{a_{1}}\frac{{PWV}^{2}}{P}}} - 1} \right)^{2}}} & \left\lbrack {{Ma}{equation}17} \right\rbrack\end{matrix}$

for pressure, P. Whose predecessor, equations

$\begin{matrix}{{P \approx {\frac{C}{2}\frac{A_{0}}{A - A_{0}}e^{\frac{{a_{1}({A - A_{0}})}^{2}}{4A_{0}^{2}}}}},} & \left\lbrack {{Ma}{equation}15} \right\rbrack\end{matrix}$ $\begin{matrix}{{PWV}^{2} \approx {\frac{Ca_{1}}{4\rho}\frac{A}{A_{0}}{e^{\frac{{a_{1}({A - A_{0}})}^{2}}{4A_{0}^{2}}}.}}} & \left\lbrack {{Ma}{equation}16} \right\rbrack\end{matrix}$

feature direct relationships between the human artery geometricparameter A, A_(o), R_(o) and h_(o); the material constants C, a₁ and ρand P and PWV. Within this system, the geometric parameters are deriveddirectly from pulsed echo measurements and material constants C, a₁ andρ are selected from well understood curves like FIG. 3A-D. Based on theforegoing relationships as described by Ma, et al. and incorporatedherein, embodiments disclosed herein employ and improve upon theconcepts suggested by Ma et al. in an implanted MEMS sensor that isinjected near the target vessel.

Using at least two sensor arrays, for example as in sensor implant 102b, shown in FIG. 2B, vessel dimensions as well as PWV can be determinedas illustrated in FIG. 12 . With appropriate signal processing andfocusing of the US beams, four separate US pulses can be defined,representing the outer surface of the near (proximal) wall, the innersurface of the near (proximal) wall, the inner surface of the far(distal) wall, and the outer surface of the far (distal) wall. Thisallows determination of not only the diameter of the inner vessel, butalso the thickness of the arterial wall. Heart rate is also directlydeterminable from this signal over time. Table 1 sets forth theparameters identified in FIG. 12 .

TABLE 1 FIG. 12 parameters Dimensions Peaks OD outside diameter no nearwall, outside ID inside diameter ni near wall, inside WT wall thicknessfi far wall, inside ΔT time of travel of BP pulse from fo far wall,outside sensor 1 to sensor 1 as identified by wall movement

Using these US measurements, plus the known distance between sensor 1and sensor 2, the PWV can be calculated as PWV=(d)/ΔT. It is to be notedthat the pulse echo shown can be the statistical sum of pulse echoreceived from several sensors and reflects all pre-processing completedin hardware.

FIG. 13 depicts an embodiment of a process flow for determination ofpatient blood pressure and general hemodynamic state. Placement ofsensor implants 102 according to the present disclosure as describedabove may be performed as an in- or outpatient procedure, employingclinically accepted practices for subcutaneous insertion. Typicalplacement sites include the upper arm targeting the brachial artery formonitoring, or the thoracic region targeting the subclavian artery inthe delta pectoral groove for monitoring. At time of placement (step185), patient diastolic blood pressure is measured and input to thesystem, for example via interface 110 (step 186). Other patient data maybe input at this time to improve accuracy of hemodynamic stateassessment. Such other information may include patient age, sex, weight,height and any known comorbidities. After sensor implant placement isverified, the system is initialized (step 187). At this stage,monitoring begins with US sensor modules 124 and status sensor module130 (step 188). At a minimum, body position or changes in body positionare detected (step 188) with an accelerometer included in status sensormodule 130 to permit adjustment of the calculated blood pressure to takeinto account variations based on body position and movement. Sensormodule operation may be programmed on an intermittent basis at specificperiods or may be continuous or near-continuous.

US pulse echo signals, as shown in FIG. 12 , are received (step 189)initially by electronics sub-module 135 for processing in control andsignal processing module 123. In some embodiments, processing at thispoint may be minimal, such as filtering and signal amplification, withthe signal data thereafter transmitted via communications module forfurther signal processing in external module 106 or in other networkedprocessing environments such as network-based systems 108 or a computingsystem associated with user interface 110. Alternatively, in morepreferred embodiments, further signal processing as described in thefollowing steps 190-194 is executed within control and signal processingmodule 123 of sensor implant 102 according to instructions stored inmemory sub-module 133. Regardless of locus of execution, envelopedetection (step 190), region-of-interest (ROI) detection (step 191), andpeak detection (step 192) are executed in accordance with knownsignal-processing algorithms for processing of US signals. A variety ofsuch algorithms are well-known in the art and may be selected by personsof ordinary skill based in the teaching contained herein. With signaldata appropriately processed for interpretation by the designatedcomputing device (internal, external or networked), vessel diameter as afunction of time is determined based on analysis of the US signals (step193). Measured and recorded data stored in memory module 133 mayinclude, for example, vessel inner and outer diameters at each US sensorarray, ΔT between the different US sensor array readings, heartrate/interval, temperature and patient or sensor implant orientation.

Pulse wave velocity (PWV) is determined and recorded at step 194 basedon parameters determined in prior steps. Based on determined PWV and atleast the previously measured and entered Diastole BP (step 186), bloodpressure is calculated (step 195), according to correlations known inthe art, for example, using algorithms described by Ma et al. asexplained above. Additional inputs to blood pressure calculation (step195), which may increase accuracy of the calculated blood pressure, mayinclude other measured parameters (step 188) such as patient activity ororientation (as determined by accelerometer or IMU in status sensormodule 130) and body temperature (as determined by temperature sensor inmodule 130). Other parameters as described hereinabove also may befactored in by persons of ordinary skill based on the teachings of thepresent disclosure. Patient blood pressure and other hemodynamicparameters as measured and determined, along with measured parameters(step 188) are delivered to the clinician/patient interface, such asinterface 110 (step 196). In one embodiment, calculation of bloodpressure is executed in network-based systems through appropriatenetwork connections with local control module 106.

FIG. 14 illustrates a further alternative embodiment of a system 100 aaccording to the present disclosure. In this example, sensor implant 102includes at least two ultrasound sensor modules comprised ofmicromachined ultrasonic transducer arrays, a status sensor modulecomprised of at least an accelerometer, and a control module includingat least one microprocessor and at least one memory containinginstructions and configured to allow the sensor implant to perform atleast sensing and processing steps 188 through 193. In this specificexample, communication module 122 uses Bluetooth communication totransmit a processed data stream containing blood vessel dimension,timing and accelerometer information as needed to permit calculation ofpulse wave velocity and patient blood pressure. In this example, apersonal mobile device is configured as one or both of local module 106and patient interface 110 using a mobile device app and transmits theprocessed data stream to a networked computer for calculation of pulsewave velocity and patient blood pressure according to stored algorithmsdiscussed herein. Patient blood pressure information is conveyed back tothe patient via the mobile device 106/110. Optionally, a separateclinician interface may receive the patient data directly from networkedcomputing device 108 via the network or through the patient mobiledevice 106/110.

Parameters utilized in processing may include those parameters that aredetermined during initial implantation of implant sensor 102 and as maybe updated as needed with periodic calibration. In some embodimentsperiodic calibration may include analysis to determine placementrelative to initial placement location. Given the unique implantstructure employing, in some embodiments (e.g. sensor implants 102 b and102 c), multiple sensor MUT modules positioned at known fixed distanceswith respect to one another, analysis of returned US signals allows forcontinually accurate PWV calculation by using changes in the US-viewedorientation relative to the observed vascular structure to determine askew factor for correcting PWV calculations. For example, usinganatomical markers as detected by sensor modules 124 and interpreted bycontrol and signal processing module 123, the system may determine thatthe longitudinal axis of the sensor implant, originally preferablyimplanted in alignment with direction of blood flow or at a knownorientation with respect thereto, has become skewed relative to flowdirection by a determined skew angle. The system may then recalculatethe distance between N and N+1 sensor modules 124 as (cos[skewangle])/[fixed sensor module spacing]=[skew adjusted sensor spacing].

As will be appreciated by persons skilled in the art, devices, systemsand methods disclosed herein, given the large and varied amount ofphysiological and specifically hemodynamic data generated, allow foraccurate detection and classification of arrythmias, such asbradycardia, ventricular tachy-cardia, atrial fibrillation, atrialtachycardia, and sinus pause using data generated in accordance with theteaching of the present disclosure in known diagnostic algorithms.Further, one or more of the following vital signals: systolic BP,diastolic BP, mean arterial BP, Pulse Wave Velocity (PWV), blood flow,arterial stiffness, elasticity modulus, ECG waveform, heart rate, heartrhythm, atrial fibrillation, bradycardia, tachycardia, sinus pause,activity, body position, blood pressure variability, heart ratevariability, endothelial function, coronary artery disease, blood oxygensaturation (O2 sat), composite score or indication of cardiovascularhealth and risk may be calculated, stored and uploaded to network-basedsystems for accurate patient assessments over extended times withoutrequiring in-patient or clinic visits for data collection. In a furtheraspect of the present disclosure, patient-centered engagement appsemploying user interfaces on mobile devices or home computing devices toencourage adherence and patient behaviors may be driven based oncollected data and analysis thereof.

In some embodiments, various aspects of the present disclosure,including, for example, local module 106, network-based modules 108,clinician user interface/application 110, and control and signalprocessing module 123 among others, may be executed as one or morecomputing devices 200 as illustrated in FIG. 15 . In this example,computing device 200 includes one or more processors 202, memory 204,storage device 206, high-speed interface 208 connecting to memory 204and high-speed expansion ports 210, and a low speed interface 212connecting to low speed bus 214 and storage device 206. Each of thecomponents 202, 204, 206, 208, 210, and 212, are interconnected usingvarious busses or other suitable connections as indicated in FIG. 15 byarrows connecting components. Processor 202 can process instructions forexecution within the computing device 200, including instructions storedin the memory 204 or on the storage device 206 to display graphicalinformation via GUI 218 with display 220, or on an external userinterface device, coupled to high speed interface 208. In otherimplementations, multiple processors and/or multiple busses may be used,as appropriate, along with multiple memories and types of memory. Also,multiple computing devices 200 may be connected, with each deviceproviding portions of the necessary operations (e.g., as a server bank,a group of blade servers, or a multi-processor system).

Memory 204 stores information within the computing device 200. In oneimplementation, the memory 204 is a computer-readable medium. In oneimplementation, the memory 204 is a volatile memory unit or units. Inanother implementation, the memory 204 is a non-volatile memory unit orunits. Memory within implant 102 may store, for example data fromultrasound readings representing vessel dimensions and sensor timing andpatient movement based on accelerometer data. Such data also maycomprise a data stream communicated from the sensor implant computingdevice and may be stored in a network-based memory along with pulse wavevelocity and blood pressure calculations executed in a network-basedcomputing device.

Storage device 206 is capable of providing mass storage for thecomputing device 200, and may contain information such as the databaseof tile display information described hereinabove. In oneimplementation, storage device 206 is a computer-readable medium. Invarious different implementations, storage device 206 may be a floppydisk device, a hard disk device, an optical disk device, or a tapedevice, a flash memory or other similar solid state memory device, or anarray of devices, including devices in a storage area network or otherconfigurations. In one implementation, a computer program product istangibly embodied in an information carrier. The computer programproduct contains instructions that, when executed, perform one or moremethods, such as those described above. The information carrier is acomputer- or machine-readable medium, such as the memory 204, thestorage device 206, or memory on processor 202.

High speed controller 208 manages bandwidth-intensive operations for thecomputing device 200, while low speed controller 212 manages lowerbandwidth-intensive operations. Such allocation of duties is exemplaryonly. In one implementation, high-speed controller 208 is coupled tomemory 204, display 220 (e.g., through a graphics processor oraccelerator), and to high-speed expansion ports 210, which may acceptvarious expansion cards (not shown). In the implementation, low-speedcontroller 212 is coupled to storage device 206 and low-speed expansionport 214. The low-speed expansion port, which may include variouscommunication ports (e.g., USB, Bluetooth, Ethernet, wireless Ethernet)may be coupled to one or more input/output devices as part of GUI 218 oras a further external user interface, such as a keyboard, a pointingdevice, a scanner, or a networking device such as a switch or router,e.g., through a network adapter.

Various implementations of the systems and techniques described here canbe realized in digital electronic circuitry, integrated circuitry,specially designed ASICs (application specific integrated circuits),computer hardware, firmware, software, and/or combinations thereof.These various implementations can include implementation in one or morecomputer programs that are executable and/or interpretable on aprogrammable system including at least one programmable processor, whichmay be special or general purpose, coupled to receive data andinstructions from, and to transmit data and instructions to, a storagesystem, at least one input device, and at least one output device.

These computer programs (also known as programs, software, softwareapplications or code) include machine instructions for a programmableprocessor, and can be implemented in a high-level procedural and/orobject-oriented programming language, and/or in assembly/machinelanguage. As used herein, the terms “machine-readable medium”“computer-readable medium” refers to any computer program product,apparatus and/or device (e.g., magnetic discs, optical disks, memory,Programmable Logic Devices (PLDs)) used to provide machine instructionsand/or data to a programmable processor, including a machine-readablemedium that receives machine instructions as a machine-readable signal.The term “machine-readable signal” refers to any signal used to providemachine instructions and/or data to a programmable processor.

To provide for interaction with a user, the systems and techniquesdescribed here can be implemented on a computer having a display device(e.g., an LED, OLED or LCD display) for displaying information to theuser and a keyboard and a pointing device (e.g., a mouse or a trackball)by which the user can provide input to the computer. Other kinds ofdevices can be used to provide for interaction with a user as well; forexample, feedback provided to the user can be any form of sensoryfeedback (e.g., visual feedback, auditory feedback, or tactilefeedback); and input from the user can be received in any form,including acoustic, speech, or tactile input.

The systems and techniques described here can be implemented in acomputing system that includes a back end component (e.g., as a dataserver), or that includes a middleware component (e.g., an applicationserver), or that includes a front end component (e.g., a client computerhaving a graphical user interface or a Web browser through which a usercan interact with an implementation of the systems and techniquesdescribed here), or any combination of such back end, middleware, orfront end components. The components of the system can be interconnectedby any form or medium of wired or wireless digital data communication(e.g., a communication network). Examples of communication networksinclude a local area network (“LAN”), a wide area network (“WAN”), andthe Internet.

The computing system can include clients and servers. A client andserver are generally remote from each other and typically interactthrough a communication network. The relationship of client and serverarises by virtue of computer programs running on the respectivecomputers and having a client-server relationship to each other.

Other features and advantages include that the implanted sensor systemis actively powered with a rechargeable battery that is integrated intothe implanted sensor system, which has the benefit of minimizing patientburden while allowing long-term (for months to years) of functional use.The implanted sensor system will automatically connect to the externalcharging and communication module when the patient is within range ofthe charging and communication module. When connected the externalcharging and communication system will charge the battery in theimplanted sensor system. A benefit of the active implanted sensor systemwith automatic charging is that the patient does not need to take actionto recharge the battery. The implanted sensor system has a longevity ofmonths to years.

Implanted/injectable sensor systems as disclosed herein may also storesensor signal data (for instance, up to a week) in the memory chip thatis designed into the ASIC and memory module of the implanted sensorsystem. This can further reduce the burden to the patient to be in rangeof the external charging and communication system and reduces the riskof lost data.

Disclosed delivery embodiments also provide an ability to retract andreposition the implanted/injectable sensor prior to final fixation tofind optimal sensor placement. This is due to the functions of theinjection tool in combination with the fixation design of the implantedsensor system. One benefit of this feature is to enable sensorrepositioning for optimal sensor accuracy.

Implanted/injectable sensor systems as disclosed may employ an RFcommunication module to enable transfer of implanted sensor signal datato the external charging and communication system. The RF communicationmodule optionally may be designed to support charging of the implantedsensor system.

Implanted/injectable sensors as disclosed are hermetically sealed toprotect the sensor components for longer term implantation to addresschronic conditions. The sensor package may be coated with abiocompatible material that prevents tissue growth and blood clotting.

Summary of aspects of embodiments of the present disclosure:

-   -   1. An active implantable sensor system for measuring and        recording cardiovascular signals from a blood vessel comprising        an injectable sensor module configured for delivery by injection        through a syringe-like delivery device into tissue adjacent a        blood vessel.    -   2. An active implantable sensor system for measuring and        recording cardiovascular signals from a blood vessel, including        systolic and diastolic blood pressure, and comprised of:        -   a. a sensing module that utilizes MEMS piezoelectric sensors            (ultrasound) and may also incorporate other sensors such as            a MEMS strain gauge sensor, and piezoelectric sensors;        -   b. an ASIC and memory module that processes incoming signals            and stores data for up to a week;        -   c. power and communication module that incorporates a            battery and antenna for communication and optional charging;            and        -   d. fixation design, architecture and approach that minimizes            trauma and allows for explant or repositioning.    -   3. Cardiovascular monitor is fixated outside the target blood        vessel, with:        -   a. a novel fixation mechanism that allows the device to be            repositioned, explanted, and prevents disruption or            occlusion of the vessel being monitored;        -   b. primary cell battery or rechargeable battery with at            least 6 months longevity;        -   c. wirelessly transmits data to an external            source/network-based system; and        -   d. improved bio-coating on the exterior of cardiovascular            monitor that minimizes encapsulation.    -   4. Sensing Module that:        -   a. collects sensor data every 10-30 minutes for programmed            duration (24 hours, 48 hours, 1 week, 1 month . . . );        -   b. includes MEMS diaphragm pressure sensor that measures            blood pressure and correlates to sphygmomanometer blood            pressure;        -   c. monitors and detects blood pressure, activity, body            position; and        -   d. calibrates and recalibrates pressure measurements            post-maturation phase.    -   5. Algorithm Module, with novel algorithms, that is:        -   a. physician-programmable for detection and monitoring            zones, duration and frequency of measurements, and ability            for patient to access recording.    -   6. External Patient Module that allows:        -   a. recharging of cardiovascular monitor; and        -   b. wireless transmission of raw data to cloud and Algorithm            Module.    -   7. Web-based software solution that enables physician        programming of algorithm module, and ability to review patient        cardiovascular data.

The foregoing has been a detailed description of illustrativeembodiments of the disclosure. It is noted that in the presentspecification and claims appended hereto, conjunctive language such asis used in the phrases “at least one of X, Y and Z” and “one or more ofX, Y, and Z,” unless specifically stated or indicated otherwise, shallbe taken to mean that each item in the conjunctive list can be presentin any number exclusive of every other item in the list or in any numberin combination with any or all other item(s) in the conjunctive list,each of which may also be present in any number. Applying this generalrule, the conjunctive phrases in the foregoing examples in which theconjunctive list consists of X, Y, and Z shall each encompass: one ormore of X; one or more of Y; one or more of Z; one or more of X and oneor more of Y; one or more of Y and one or more of Z; one or more of Xand one or more of Z; and one or more of X, one or more of Y and one ormore of Z.

Various modifications and additions can be made without departing fromthe spirit and scope of this disclosure. Features of each of the variousembodiments described above may be combined with features of otherdescribed embodiments as appropriate in order to provide a multiplicityof feature combinations in associated new embodiments. Furthermore,while the foregoing describes a number of separate embodiments, what hasbeen described herein is merely illustrative of the application of theprinciples of the present disclosure. Additionally, although particularmethods herein may be illustrated and/or described as being performed ina specific order, the ordering is highly variable within ordinary skillto achieve aspects of the present disclosure. Accordingly, thisdescription is meant to be taken only by way of example, and not tootherwise limit the scope of this disclosure or of the inventions as setforth in following claims.

It is claimed:
 1. A hemodynamic sensor system, comprising: a sensorimplant, comprising a housing configured and dimensioned to be placedsubcutaneously in tissue adjacent a target blood vessel in a patient,the sensor implant further comprising within the housing: at least onesensor configured to detect one or more physiological parametersindicative of patient hemodynamic condition, wherein at least one saidsensor comprises an at least one ultrasound transducer; and acommunication module communicating with the at least one sensor totransmit one or more signals comprising signals representative ofdetected physiological parameters to an external receiver.
 2. The systemof claim 1, further comprising an external, local controller configuredto (1) wirelessly receive signals transmitted by the communicationmodule, and (2) at least one of further process said signals or relaysaid signals to a network.
 3. The system of claim 1, comprising at leasttwo sensors wherein at least one said sensor comprises an accelerometerconfigured to determine movement or changes in position of the patient.4. The system of claim 1, wherein: the housing is configured along ahousing axis; and said at least one sensor comprises at least twoultrasound transducers positioned along said housing axis with a knowndistance between the at least two ultrasound transducers.
 5. The systemof claim 4, wherein the ultrasound transducers comprise micromachinedultrasonic transducers having an array of ultrasound sensor elements. 6.The system of claim 4, wherein said housing further comprises anultrasound transmissive portion aligned with each said ultrasoundtransducer.
 7. The system of claim 4, wherein each said sensor transmitsultrasound pulses that produce echo pulses received by said sensorindicative of: a change in diameter of the target blood vessel inresponse to pulsations of the cardiac cycle; and the target blood vesselnear wall outer surface, near wall inner surface, far wall innersurface, and far wall outer surface.
 8. The system of claim 7, whereinthe signals transmitted by the communication module comprise signalsindicative of: a change in diameter of the target blood vessel inresponse to a cardiac pulse at a first location detected by a first ofsaid at least two ultrasound transducers; a change in diameter of thetarget blood vessel in response to the cardiac pulse at a secondlocation detected by a second of said at least two ultrasoundtransducers; and a time difference between the changes in diameterdetected by said first and second ultrasound transducers.
 9. The systemof claim 8, further comprising at least one microprocessor and at leastone memory in operative communication with the at least onemicroprocessor, the memory containing an instruction set comprisingmachine-executable instructions that, when executed by the at least onemicroprocessor: determine pulse wave velocity for the target bloodvessel based on said diameter changes, known distance and timedifference; and determine patient blood pressure based on the determinedpulse wave velocity and a previously input patient base-line bloodpressure value.
 10. The system of claim 9, wherein the instruction setcontained in the at least one memory further comprisesmachine-executable instructions that, when executed by the at least onemicroprocessor determine target blood vessel wall thickness.
 11. Thesystem of claim 9, wherein the instruction set contained in the at leastone memory further comprises machine-executable instructions that, whenexecuted by the at least one microprocessor communicates the patientblood pressure to a user interface device.
 12. The system of claim 9,wherein said at least one memory and instruction set resides at least inpart outside the sensor implant in a network-based computing system. 13.The system of claim 9, wherein said at least one memory and instructionset resides at least in part in the external, local controller.
 14. Thesystem of claim 9, wherein said at least one memory and instruction setresides at least in part within the sensor implant housing.
 15. Ahemodynamic sensor system, comprising a sensor implant configured to beimplanted in patient tissue adjacent a target blood vessel, wherein thesensor implant comprises: a housing having a housing axis; at least twoultrasound transducers disposed in the housing along the housing axiswith a known distance along said housing axis between the at least twoultrasound transducers, each said ultrasound transducer positioned todetect a change in diameter of the target blood vessel in response to acardiac pulse and produce signals representative of detected changes indiameter; at least one accelerometer disposed in the housing configuredto detect movement or changes in position of the patient and producesignals representative of said movement or changes in position; acontroller disposed in the housing configured to detect timing of andprocess the signals from the ultrasound transducers and the at least oneaccelerometer to produce a data stream from which pulse wave velocityfor the target blood vessel and patient blood pressure can becalculated; a communication module disposed in the housing configured totransmit said data stream to an external receiver; and a power sourcedisposed in the housing operatively connected to power the sensorimplant.
 16. The system of claim 15, wherein said ultrasound transducersare configured to focus ultrasound signals on the target blood vessel atdetection distance of about 2 mm to about 50 mm from said blood vessel.17. The system of claim 16, wherein the ultrasound transducers areconfigured to focus the ultrasound signals at a detection distance ofabout 3-15 mm.
 18. The system of claim 15, further comprising anexternal controller configured to (1) wirelessly receive the data streamtransmitted by the communications module and (2) at least one ofcalculate pulse wave velocity and patient blood pressure based on thedata stream or transmit the data stream to networked computing deviceconfigured to calculate the pulse wave velocity and patient bloodpressure based on said data stream.
 19. A hemodynamic sensor system,comprising: a sensor implant configured and dimensioned to be placedsubcutaneously in tissue adjacent a target blood vessel in a patient,said sensor implant comprising at least one sensor configured togenerate a data stream from which pulse wave velocity of the targetblood vessel during a sensing period can be determined, and acommunication module communicating with the at least one sensor towirelessly transmit said data stream; and a computing device configuredto receive data contained within said data stream and determine pulsewave velocity for the target blood vessel and blood pressure for thepatient using said received data.
 20. The system of claim 19, whereinthe sensor implant further comprises a processor and a memory, saidmemory containing instructions for generating the data stream comprisinginstructions that when executed by the processor cause sensor implantto: generate ultrasound pulses and receive ultrasound pulse echoesrepresenting inner and outer walls of the target blood vessel at firstand second spaced apart sensing locations with said at least one sensor;detect changes in target blood vessel diameter at the first and secondsensing locations based on said pulse echoes; and measure time betweendetecting of a change in target blood vessel diameter at the firstsensing location and at the second sensing location.
 21. The system ofclaim 19, wherein: the data stream contains information representing thetarget blood vessel diameter at first and second spaced apart sensinglocations, changes in said vessel diameter at the first and secondsensing locations and a time between said changes in diameter at thefirst and second sensing locations; and the computing device comprises:one or more computer processors; and one or more computer readablestorage devices, wherein said one or more storage devices containprogram instructions executing a computer-implemented method comprising—determining, with the computing device, the pulse wave velocity of thetarget blood vessel during the sensing period based on said timeinformation and a known distance correlated to the spaced apart distancebetween the first and second sensing locations; determining, with thecomputing device, the patient blood pressure during the sensing periodusing a received initial patient diastolic blood pressure, thedetermined pulse wave velocity and said inner and outer wall diameterinformation for the target blood vessel; and transmitting at least thepatient blood pressure to a user interface accessible by at least one ofthe patient or a patient care provider.
 22. The system of claim 21,further comprising an external local controller configured to wirelesslyreceive signals transmitted by the communication module, and relay saidsignals to the computing device.
 23. The system of claim 22, wherein thecomputing device resides at least in part in a network-based computingsystem.
 24. The system of claim 19, wherein the at least one sensorcomprises at least one ultrasound transducer array.
 25. The system ofclaim 24, wherein the at least one ultrasound array comprises at leasttwo spaced apart ultrasound transducer arrays.
 26. The system of claim24, wherein the at least one sensor further comprises an accelerometerand a temperature sensor.
 27. The system of claim 26, wherein the sensorimplant further comprises a housing configured and dimensioned to beplaced subcutaneously in tissue adjacent a target blood vessel with saidat least one sensor and communication module disposed in the housing.28. The system of claim 27, further comprising at least one tissuefixation feature on an outer surface of the housing.
 29. A hemodynamicsensor system, comprising: a sensor implant configured and dimensionedto be placed subcutaneously within tissue adjacent a target blood vesselin a patient, said sensor implant comprising— a first ultrasoundtransducer configured and controlled to send pulses and receive pulseechoes representing inner and outer walls of the target blood vessel ata first sensing location, and to generate first data representative ofsaid first sensing location pulse echoes, at least a second ultrasoundtransducer spaced from the first ultrasound transducer configured andcontrolled to send pulses and receive pulse echoes representing innerand outer walls of the target blood vessel at a second sensing location,and to generate second data representative of said second sensinglocation pulse echoes, an accelerometer configured to detect patientmovement, and to generate third data representative of detectedmovement, a temperature sensor configured to detect patient temperature,and to generate fourth data representative of detected temperature, anda communication module configured to receive said data and wirelesslytransmit said data; a local control module external to the patientconfigured to wirelessly receive and relay the data transmitted by thecommunication module; a user interface configured to receive user inputpatient specific information comprising at least an initial patientdiastolic blood pressure; and a computing device configured to receivesaid data from the local control module and said user input patientspecific information, and to execute an instruction set to determinepulse wave velocity for the target blood vessel and blood pressure forthe patient using said data and input patient specific information. 30.The system of claim 29, further comprising a clinician interface devicewith a clinician user interface configured to input patient specificinformation to the computing device and receive determinations outputfrom the computing device; and wherein the computing device comprises anetwork-based computing system.